This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Galectin-3 is a galactose-binding mammalian protein with suggested involvement in a variety of processes, including intracellular trafficking, cell-cell and cell-matrix interactions, which modulate immune cells in chronic inflammation and metastasis of malignant cells. Therefore, there is substantial interest in structurally characterizing ligand interactions and bound-ligand geometries of galectin-3 as a basis for the design of possible anti-inflammatory and anti-cancer drugs. Standard NMR methodologies, such as those giving inter-proton distance constraints from transferred NOE data, yield some useful results, but numbers of constraints can be small when carbohydrate ligands are involved, and many of these standard methodologies fail when designed inhibitors with high binding constants and slow exchange rates are used. This collaborative project provides additional orientational constraints using new NMR methodology that measures residual dipolar couplings (RDCs), paramagnetic relaxation enhancements (PREs), and pseudo-contact shifts (PCSs) on ligands bound to the perdeuterated and lanthanide tagged carbohydrate recognition domain of galectin-3.